Trial Outcomes & Findings for REduCing Immunogenicity to PegloticasE (RECIPE) Study (NCT NCT03303989)

NCT ID: NCT03303989

Last Updated: 2022-03-16

Results Overview

Proportion of participants achieving and maintaining an sUA ≤ to 6 mg/dL through 12 weeks, compared to concurrent controls.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

12 weeks

Results posted on

2022-03-16

Participant Flow

Participant milestones

Participant milestones
Measure
Pegloticase + MMF
Participants randomized to this arm will receive pegloticase + mycophenolate mofetil. Pegloticase 8 MG/ML \[Krystexxa\]: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months. MMF: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.
Pegloticase + Placebo
Participants randomized to this arm will receive pegloticase + placebo Placebo: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months. Pegloticase 8 MG/ML \[Krystexxa\]: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.
Overall Study
STARTED
24
11
Overall Study
COMPLETED
22
10
Overall Study
NOT COMPLETED
2
1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

REduCing Immunogenicity to PegloticasE (RECIPE) Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Pegloticase + MMF
n=22 Participants
Participants randomized to this arm will receive pegloticase + mycophenolate mofetil. Pegloticase 8 MG/ML \[Krystexxa\]: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months. MMF: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.
Pegloticase + Placebo
n=10 Participants
Participants randomized to this arm will receive pegloticase + placebo Placebo: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months. Pegloticase 8 MG/ML \[Krystexxa\]: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.
Total
n=32 Participants
Total of all reporting groups
Age, Continuous
55 years
STANDARD_DEVIATION 9.4 • n=99 Participants
55.5 years
STANDARD_DEVIATION 10.7 • n=107 Participants
55.2 years
STANDARD_DEVIATION 9.7 • n=206 Participants
Sex: Female, Male
Female
3 Participants
n=99 Participants
1 Participants
n=107 Participants
4 Participants
n=206 Participants
Sex: Female, Male
Male
19 Participants
n=99 Participants
9 Participants
n=107 Participants
28 Participants
n=206 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
22 Participants
n=99 Participants
10 Participants
n=107 Participants
32 Participants
n=206 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Race (NIH/OMB)
American Indian or Alaska Native
1 Participants
n=99 Participants
0 Participants
n=107 Participants
1 Participants
n=206 Participants
Race (NIH/OMB)
Asian
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
1 Participants
n=99 Participants
0 Participants
n=107 Participants
1 Participants
n=206 Participants
Race (NIH/OMB)
Black or African American
5 Participants
n=99 Participants
0 Participants
n=107 Participants
5 Participants
n=206 Participants
Race (NIH/OMB)
White
15 Participants
n=99 Participants
10 Participants
n=107 Participants
25 Participants
n=206 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Region of Enrollment
United States
22 participants
n=99 Participants
10 participants
n=107 Participants
32 participants
n=206 Participants
American College of Rheumatology / European League Against Rheumatism Flare Criteria Score
13.5 Score on a scale
STANDARD_DEVIATION 2.8 • n=99 Participants
13.8 Score on a scale
STANDARD_DEVIATION 2.7 • n=107 Participants
13.5 Score on a scale
STANDARD_DEVIATION 2.6 • n=206 Participants
Gout Flare History (flare within the last year)
Yes
15 Participants
n=99 Participants
5 Participants
n=107 Participants
20 Participants
n=206 Participants
Gout Flare History (flare within the last year)
No
7 Participants
n=99 Participants
5 Participants
n=107 Participants
12 Participants
n=206 Participants
Duration of Gout
13.3 years
STANDARD_DEVIATION 9.8 • n=99 Participants
13.4 years
STANDARD_DEVIATION 7.4 • n=107 Participants
13.4 years
STANDARD_DEVIATION 9.0 • n=206 Participants
PROMIS Pain Intensity
50.8 units on a scale
STANDARD_DEVIATION 11.3 • n=99 Participants
45.0 units on a scale
STANDARD_DEVIATION 12.4 • n=107 Participants
49.0 units on a scale
STANDARD_DEVIATION 11.8 • n=206 Participants
PROMIS Physical Function
37.5 units on a scale
STANDARD_DEVIATION 7.8 • n=99 Participants
33.8 units on a scale
STANDARD_DEVIATION 6.4 • n=107 Participants
36.3 units on a scale
STANDARD_DEVIATION 8.6 • n=206 Participants
Gout Impact Score
45.7 Score on a scale
STANDARD_DEVIATION 7.5 • n=99 Participants
46.4 Score on a scale
STANDARD_DEVIATION 7.1 • n=107 Participants
45.9 Score on a scale
STANDARD_DEVIATION 7.3 • n=206 Participants
Serum Urate Level
8.9 mg/dL
STANDARD_DEVIATION 1.8 • n=99 Participants
9.8 mg/dL
STANDARD_DEVIATION 1.3 • n=107 Participants
9.2 mg/dL
STANDARD_DEVIATION 1.7 • n=206 Participants
Body Mass Index
25 to < 30
3 Participants
n=99 Participants
1 Participants
n=107 Participants
4 Participants
n=206 Participants
Body Mass Index
30 to < 45
18 Participants
n=99 Participants
7 Participants
n=107 Participants
25 Participants
n=206 Participants
Body Mass Index
≥45
1 Participants
n=99 Participants
2 Participants
n=107 Participants
3 Participants
n=206 Participants
Comorbidities
Diabetes Mellitus /Metabolic Syndrome · Yes
3 Participants
n=99 Participants
2 Participants
n=107 Participants
5 Participants
n=206 Participants
Comorbidities
Diabetes Mellitus /Metabolic Syndrome · No
19 Participants
n=99 Participants
8 Participants
n=107 Participants
27 Participants
n=206 Participants
Comorbidities
Cerebral Vascular Vascular Disease/Heart Accident/Peripheral Vascular Disease · Yes
8 Participants
n=99 Participants
6 Participants
n=107 Participants
14 Participants
n=206 Participants
Comorbidities
Cerebral Vascular Vascular Disease/Heart Accident/Peripheral Vascular Disease · No
14 Participants
n=99 Participants
4 Participants
n=107 Participants
18 Participants
n=206 Participants
Comorbidities
Systemic Hypertension · Yes
18 Participants
n=99 Participants
7 Participants
n=107 Participants
25 Participants
n=206 Participants
Comorbidities
Systemic Hypertension · No
4 Participants
n=99 Participants
3 Participants
n=107 Participants
7 Participants
n=206 Participants
Comorbidities
Dyslipidemia · Yes
8 Participants
n=99 Participants
4 Participants
n=107 Participants
12 Participants
n=206 Participants
Comorbidities
Dyslipidemia · No
14 Participants
n=99 Participants
6 Participants
n=107 Participants
20 Participants
n=206 Participants
Comorbidities
Kidney Stones · Yes
4 Participants
n=99 Participants
5 Participants
n=107 Participants
9 Participants
n=206 Participants
Comorbidities
Kidney Stones · No
18 Participants
n=99 Participants
5 Participants
n=107 Participants
23 Participants
n=206 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: 32 participants received at least one dose of pegloticase and were included in modified intention-to-treat analyses.

Proportion of participants achieving and maintaining an sUA ≤ to 6 mg/dL through 12 weeks, compared to concurrent controls.

Outcome measures

Outcome measures
Measure
Pegloticase + MMF
n=22 Participants
Participants randomized to this arm will receive pegloticase + mycophenolate mofetil. Pegloticase 8 MG/ML \[Krystexxa\]: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months. MMF: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.
Pegloticase + Placebo
n=10 Participants
Participants randomized to this arm will receive pegloticase + placebo Placebo: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months. Pegloticase 8 MG/ML \[Krystexxa\]: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.
Proportion of Participants Achieving and Maintaining an sUA ≤ to 6 Milligram Per Deciliter (mg/dL) Through 12 Weeks
Yes
19 Participants
4 Participants
Proportion of Participants Achieving and Maintaining an sUA ≤ to 6 Milligram Per Deciliter (mg/dL) Through 12 Weeks
No
3 Participants
6 Participants

Adverse Events

Pegloticase + MMF

Serious events: 2 serious events
Other events: 15 other events
Deaths: 0 deaths

Pegloticase + Placebo

Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Pegloticase + MMF
n=22 participants at risk
Participants randomized to this arm will receive pegloticase + mycophenolate mofetil. Pegloticase 8 MG/ML \[Krystexxa\]: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months. MMF: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.
Pegloticase + Placebo
n=10 participants at risk
Participants randomized to this arm will receive pegloticase + placebo Placebo: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months. Pegloticase 8 MG/ML \[Krystexxa\]: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.
Skin and subcutaneous tissue disorders
Infusion Reaction
0.00%
0/22 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.
10.0%
1/10 • Number of events 1 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.
Injury, poisoning and procedural complications
Motor Vehicle Crash
4.5%
1/22 • Number of events 1 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.
0.00%
0/10 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.
Cardiac disorders
Chest Pain
4.5%
1/22 • Number of events 1 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.
0.00%
0/10 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.
Gastrointestinal disorders
Abdominal Pain
4.5%
1/22 • Number of events 1 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.
0.00%
0/10 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.

Other adverse events

Other adverse events
Measure
Pegloticase + MMF
n=22 participants at risk
Participants randomized to this arm will receive pegloticase + mycophenolate mofetil. Pegloticase 8 MG/ML \[Krystexxa\]: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months. MMF: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.
Pegloticase + Placebo
n=10 participants at risk
Participants randomized to this arm will receive pegloticase + placebo Placebo: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months. Pegloticase 8 MG/ML \[Krystexxa\]: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.
Cardiac disorders
Cardia
9.1%
2/22 • Number of events 2 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.
10.0%
1/10 • Number of events 1 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.
Gastrointestinal disorders
Gastrointestinal
18.2%
4/22 • Number of events 4 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.
10.0%
1/10 • Number of events 1 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.
Infections and infestations
Infections
9.1%
2/22 • Number of events 2 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.
0.00%
0/10 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.
Musculoskeletal and connective tissue disorders
Musculoskeletal (arthralgia, myalgia, low back pain, orthopedic trauma, bursitis tendonitis)
40.9%
9/22 • Number of events 19 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.
10.0%
1/10 • Number of events 2 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.
Skin and subcutaneous tissue disorders
Skin
9.1%
2/22 • Number of events 2 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.
10.0%
1/10 • Number of events 1 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.
General disorders
Other (Lab abnormality, anxiety, neurological, and oral pain)
40.9%
9/22 • Number of events 11 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.
50.0%
5/10 • Number of events 5 • 36 weeks
Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.

Additional Information

Jeff Foster

UNIVERSITY OF ALABAMA AT BIRMINGHAM

Phone: 2059966086

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: OTHER